The use of so-called non-steroidal abtiinflammatory drugs ("NSAID's") for inhibiting cyclooxygenase is well known (see J. Lombardino in "Nonsteroidal Antiinflammatory Drugs", Wiley-Interscience, New York, 1985).
The enzyme 5-lipoxygenase catalyzes the first step leading to the biosynthesis of all the leukotrienes and therefore inhibition of this enzyme provides an approach to limit the effects of all the products of this pathway. Products of the 5-lipoxygenase cascade are extremely potent substances which produce a wide variety of biological effects, often in the nanomolar to picomolar concentration range (Sirois, P. Pharmacology of the Leukotrienes. Advances in Lipid Research. R. Paoletti, D. Kritchevesky, editors, Academic Press, 21: 79, 1985). Leukotrienes have been reported to be important mediators in several disease states including asthma, allergic rhinitis, rheumatoid arthritis, gout, psoriasis, adult respiratory disease syndrome, inflammatory bowel disease, endotoxin shock, ischemia-induced myocardial injury, central nervous pathophysiology, and atherosclerosis. Agents capable of abrogating the effects of these potent mediators of pathophysiological processes represent a promising class of therapeutic agents (Brooks, D. W., Bell, R. L., and Carter, G. W. Chapter 8. Pulmonary and Antiallergy Agents, Annual Reports in Medicinal Chemistry, Allen, R. C. ed., Academic Press 1988).
Formulations comprising a combination or mixture of non-steroidal antiinflammatory drugs (NSAID) and 5-lipoxygenase inhibitors have been described by Wellcome (WO 90/01929).